Study of Sacituzumab Govitecan in Participants With Urothelial Cancer That Cannot Be Removed or Has Spread

  • Interventional
  • Recruiting
  • NCT03547973
Eligibility Details Visit

A Phase II Open-Label Study of Sacituzumab Govitecan in Unresectable Locally Advanced/Metastatic Urothelial Cancer

The objective of this study is to evaluate the efficacy and safety of sacituzumab govitecan-hziy monotherapy and with novel combinations in participants with metastatic urothelial cancer (mUC).

Non-Randomized for Cohorts 1,2,3, and 4; Randomized for Cohorts 5 and 6. Cohort 5 has been cancelled, effective December 2023.


Age Group
18 Years and up

Accepting Healthy Volunteers?

Key Inclusion Criteria:

         - Female or male individuals, ≥ 18 years of age (19 Years old for South Korea).

         - Individuals with histologically confirmed urothelial cancer (UC).

         - Eastern Cooperative Oncology Group (ECOG) Performance status score of 0 or 1.

         - Cohort 1: Have had progression or recurrence of urothelial cancer following receipt of platinum-containing regimen (cisplatin or carboplatin):

             - Received a first-line platinum-containing regimen in the metastatic setting or for inoperable locally advanced disease;

             - Or received neo/adjuvant platinum-containing therapy for localized muscle-invasive urothelial cancer, with recurrence/progression ≤12 months following completion of therapy.

         - Cohort 1: In addition to above criterion, have had progression or recurrence of urothelial cancer following receipt of an Anti-programmed Cell Death Protein 1 (anti-PD-1)/ Anti-programmed Death Ligand 1 (PD-L1) therapy.

         - Cohort 2: Were ineligible for platinum-based therapy for first line metastatic disease and have had progression or recurrence of urothelial cancer after a first-line therapy for metastatic disease with anti-PD-1/PD-L1 therapy. Individual may not have received any platinum for treatment of recurrent, metastatic or advanced disease.

         - Cohort 3: Progression or recurrence of UC following a platinum containing regimen in the metastatic setting, or progression or recurrence of UC within 12 months of completion of platinum-based therapy as neoadjuvant or adjuvant therapy.

         - Cohort 4: Individual has not received any platinum-based chemotherapy in the metastatic or unresectable locally advanced setting. Creatinine clearance of at least 50 mL/min calculated by Cockcroft-Gault formula or another validated tool. For individuals receiving cisplatin at 70 mg/m^2 on Day 1 of every 21-day cycle, a creatinine clearance of least 60 mL/min calculated by Cockcroft -Gault formula or another validated tool is required. Individuals with creatinine clearance between 50 to 59 mL/min are to receive a split dose of cisplatin (35 mg/m^2 Day 1 and Day 8 of every 21-day cycle).

         - Cohorts 4, 5, 6: Archival tumor tissue comprising muscle-invasive or metastatic urothelial carcinoma, or a biopsy of metastatic urothelial carcinoma.

         - Cohort 5: Individuals received at least 4 cycles and no more than 6 cycles of GEM + cisplatin. No other chemotherapy regimens are allowed in this cohort, with the exception of prior adjuvant or neoadjuvant systemic therapy with curative intent after > 12 months from completion of therapy.

             - No evidence of progressive disease following completion of first-line chemotherapy (ie, CR, PR, or SD per RECIST v1.1 guidelines as per investigator).

             - Treatment-free interval of 4 to 10 weeks since the last dose of chemotherapy.

         - Cohort 6: Cis-ineligible and no prior therapy for metastatic disease or for unresectable locally advanced disease. Checkpoint inhibitor therapy naïve or >12 months from completion of adjuvant therapy are permitted.

         - Cohorts 4 and 6: Have measurable disease by CT or MRI as per RECIST 1.1 criteria. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.

         - Cohorts 1, 2, 3 and 5: Creatinine clearance ≥ 30 mL/min as calculated by the Cockcroft-Gault formula unless otherwise specified

         - Adequate renal and hepatic function.

         - Adequate hematologic parameters without transfusional support.

         - Individuals must have a 3-month life expectancy.

        Key Exclusion Criteria:

         - Females who are pregnant or lactating.

         - Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.

         - Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (ie, ≤Grade 1 from AEs due to a previously administered agent).

         - For Cohort 5: Alopecia, sensory neuropathy Grade ≤2 is acceptable, or other Grade < 2 adverse events not constituting a safety risk based on the investigator's judgment are acceptable.

         - Requires concomitant medication interfering with UGT1A1 with no alternate option available.

         - Has an active second malignancy.

         - Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.

         - Has known active Hepatitis B or Hepatitis C.

         - Has other concurrent medical or psychiatric conditions.

         - Cohort 3: Has received anti-PD-1/PD-L1 therapy previously.

         - Cohorts 3 to 5: Has an active autoimmune disease that required systemic treatment in past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.

         - Cohorts 3 to 6: Has received a live vaccine within 30 days prior to the first dose of study drug(s), has history or evidence of interstitial lung disease (ILD) or non-infectious pneumonitis.

         - Cohort 4: Refractory to platinum (i.e., relapsed ≤ 12 months after completion of chemotherapy) in the neoadjuvant/adjuvant setting.

         - Cohorts 4, 5, and 6: For individuals who received prior CPI, a treatment-free interval >12 months between the last treatment administration and the date of recurrence is required.

        Note: Other protocol defined Inclusion/Exclusion criteria may apply.

At a Glance

National Government IDNCT03547973


Lead SponsorGilead Sciences

Lead PhysicianRandy Sweis


18 Years and up